National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS)

Purpose

This Notice informs potential applicants of changes in the
NIAMS policies and procedures for the acceptance, peer review, and funding of
investigator-initiated clinical trials.

Overview

The NIAMS is committed to improving the health of patients
with rheumatic, musculoskeletal, and skin diseases by supporting
investigator-initiated clinical trials that lead to better clinical
outcomes. The NIAMS’ goal is to identify and fund trials that are as
timely and informative as possible, and which will lead to improvements in
clinical practice for disease prevention, diagnosis, and treatment. To
this end, the NIAMS has enhanced its clinical trials program.

Background

The NIAMS will support investigator-initiated clinical
trials through a two part grant process: (1) a clinical trial planning grant
(U34) followed by (2) a clinical trial implementation cooperative agreement (UM1).
Pilot and feasibility studies to support and enable the initiation of clinical
trials will be supported by the R21 mechanism.

Clinical trials range from small first-in-human or
tolerability studies to larger trials of efficacy or effectiveness. The NIAMS
has redesigned its clinical trials program in order to support the spectrum of
such studies with funding mechanisms tailored to different levels of
complexity. Investigators planning trials that involve few subjects and limited
duration of follow-up may apply for a NIAMS Pilot and Feasibility Clinical
Research Grant (R21). For trials involving greater numbers of subjects or of
greater complexity or risk, investigators should apply for funding through a
NIAMS Clinical Trial Implementation Cooperative Agreement (UM1). These larger
and more complex trials require substantial planning and preparation prior to
opening for recruitment, and investigators are expected to apply for a NIAMS
Clinical Trial Planning Grant (U34) prior to submitting an application for the UM1
to implement the trial. The planning grant will allow an investigator to
accomplish the planning activities (manual of operating procedures, FDA
approvals, etc) which are often necessary for actually implementing a clinical
trial; applicants for a Clinical Trial Implementation Cooperative Agreement are
expected to be able to begin the trial without further planning activities when
the UM1 is awarded. Investigators who have already completed planning
activities either by a previously awarded NIAMS U34, R34, or other means may
also submit a UM1 implementation grant, but are strongly encouraged to consult
with NIAMS staff in advance. Investigators considering applying to the NIAMS
for a clinical trial grant should refer to the NIAMS
Clinical Trials Policy web site. The program announcements for Pilot and
Feasibility Clinical Research Grants (R21), Clinical Trial Planning Grants
(U34), and Clinical Trial Implementation Cooperative Agreements (UM1) are
available through the links below.

Prior consultation with the NIAMS is strongly encouraged for
submission of the NIAMS Clinical Trial Implementation (UM1) Grant application,
including new and resubmission applications. NIAMS staff will consider whether
the proposed clinical trial meets the goals and mission of the Institute and
whether it is appropriate to conduct it as an investigator-initiated clinical
trial, but will not evaluate the technical and scientific merit of the proposed
trial. Technical and scientific merit will be determined during peer review.
In the presubmission consultation phase, if the proposed trial does not meet
the goals and mission of the NIAMS, applicants will be so informed. If the
NIAMS ascertains that substantial additional planning may be necessary,
submission of the application may be considered under the Clinical Trial
Planning Grant (U34) Cooperative Agreement FOA (PAR-11-169).
The NIAMS reserves the right to determine that support for clinical trials may
be directed through other available mechanisms supported by the NIAMS.

Applicants are also strongly encouraged to submit a Letter of Intent (LOI)
to the NIAMS before submission of an application for
either a U34 or a UM1, including
new and resubmission applications. Investigators may refer to the NIAMS
website for details on the information
to be included in the LOI. Applicants are
encouraged to allow enough time before the planned receipt date to give the Institute at
least 10 weeks, particularly if there has been no prior consultation
with the NIAMS about the application. LOI should be
submitted to the Scientific/Research
contacts listed in the FOA who will
share the request with the appropriate Program Official.

Peer review of properly completed applications submitted in
response to the Program Announcements for the clinical trials R21, U34 and UM1
will be conducted by the NIAMS Arthritis and Musculoskeletal and Skin Diseases
Clinical Trials Review Committee (AMSCT).

The Pilot and Feasibility Clinical Research Grants are
designed to allow initiation of exploratory, short-term clinical studies in
support of the development of clinical trials using a mechanism to facilitate
the development of new ideas which may be investigated without stringent
requirements for preliminary data. Proposed studies should focus on research
questions that are likely to gather critical preliminary data in support of a
future, planned clinical trial or to benefit clinical research and trials more
broadly, such as by demonstrating the feasibility of a recruitment target or
approach, obtaining data in support of potential inclusion and exclusion
criteria, or to gather preliminary evidence of efficacy, tolerability and/or
toxicity of an available drug, biologic or device in a new population relevant
to the NIAMS mission.

The U34 grant will provide support to establish the research
team, develop tools for data management and oversight of the research, define
recruitment strategies, develop and finalize the clinical protocol and all
essential elements of the study required for the clinical trial. The Clinical
Trial Planning Grant is not designed for the collection of preliminary data or
the conduct of pilot studies to support the rationale for a clinical trial. The
NIAMS R21 FOA (see above) will support pilot studies.

It is expected that receipt of a U34 grant will lead to the
timely submission of an application for support of the appropriate clinical
trial, incorporating the elements developed under the planning grant. The U34
application should propose planning and administrative tasks that, when
accomplished, will serve as indicators of progress in the planning phase. The NIAMS
will consult with the investigators prior to any award to identify specific
milestones (see NIAMS
clinical trial milestones website). Once certain, pre-specified
milestones are met, the investigators may consider submission of an application
for a UM1 to support implementation of the clinical trial. However, prospective
applicants should note that receipt of a Clinical Trial Planning Grant award
does not guarantee or imply funding for a subsequent clinical trial
implementation application.

The product of an awarded U34 planning
grant that has met its milestones, as submitted in the application and agreed upon by the Principal Investigator and NIH Program Official,
will be an application (UM1) to conduct the
clinical trial, which incorporates the elements developed under the planning
grant.

The NIAMS will only consider funding applications for
implementation of investigator-initiated clinical trials from U34 awardees,
unless the necessary pre-trial tasks have been completed through a R34 or other
means and it is clear that the trial implementation can begin when the UM1 is
awarded In cases where an applicant has not carried out the planning activities
with the support of a NIAMS U34, investigators are strongly encouraged to discuss
the potential clinical trial with the Program Director well in advance of submitting
the application for a UM1. Please refer to (NIAMS
website) for details as to the planning and administrative tasks that
should be complete prior to submitting a UM1 application.

Pre-approval of an application which will have direct costs
of $500,000 or more in any given year is required per
NIH policy. Applicants should go to (NIAMS website) for
information about what to include in their Letter of Request and are
encouraged to contact their program
director for additional guidance. Investigators
should allow enough time before their planned receipt date to give the
Instiutte at least 10 weeks to determine whether it will approve the written
request to submit the UM1. An
approval letter to submit the application may be
obtained from the approvpirate NIAMs Division Director and should be included
with the application.

A clinical trial implementation cooperative agreement
application should describe all necessary components to successfully conduct a
clinical trial. Implementation support is defined as support for activities
related to the conduct of the clinical trial.

Other
FOAs:

Any applications dealing with mechanistic studies in
clinical trials of immunomodulatory interventions for immune-mediated diseases
should be submitted to the NIAID Hyperaccelerated Award Program for Ancillary
Studies in Immunomodulation Clinical Trials (RFA-AI-10-014)
in which the NIAMS is a participating Institute.

Investigators should consider RFA-AR-11-013 for ancillary studies that are exploratory/ developmental and highly innovative
in nature and related to the NIAMS mission. Such studies must be in
conjunction with privately or publicly funded, large, ongoing clinical projects
and meet time-sensitivity requirements.

Effective immediately, the NIAMS will no longer participate
in or accept applications submitted under PA-09-186,
NIH Clinical Trial Planning Grant Program (R34).

This policy does not cover clinical trial applications in
response to a Request for Applications (RFA), which will follow the guidelines
and instructions in the Funding Opportunity Announcement (FOA).